This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The Resource for Biocomputing, Visualization and Informatics (RBVI) develops innovative methods and algorithms for computational and visualization-based data analysis, implements these as professional-quality, easy-to-use software tools, and applies the tools toward solving a wide range of problems relating to molecular sequence, structure, and function. UCSF Chimera (www.cgl.ucsf.edu/chimera) is the molecular modeling package under active development by the RBVI. Chimera is a tool for visualization and analysis of biomolecular structures and interactions. In addition to atomic coordinates, it can be used to explore other data types such as electron density maps, electrostatic potential maps, and sequence alignments, and it can be used to create high-quality images and movies for publication and presentation. For exploring broader biological contexts, RBVI also develops and distributes plugins to the open-source network visualization tool Cytoscape. Protein sequence or structure similarity networks, metabolic pathways, and networks of small molecule metabolites or drugs are a few examples of systems of interest. The plugins provide capabilities for manipulating and analyzing the networks and linking them to 3D visualization with Chimera. The Structure-Function Linkage Database (sfld.rbvi.ucsf.edu) connects evolutionarily related sequences and structures (superfamilies of enzymes) to their chemical reactions, and correlates conserved active site residues with specific partial reactions common to the members of a superfamily. It provides highly curated information on mechanistically diverse superfamilies, which catalyze many different overall reactions and have historically been subject to many annotation problems. This public resource can be used to guide functional annotation and protein engineering applications. The Sequence Analysis and Consulting Service (SACS, www.sacs.ucsf.edu) provides expertise in bioinformatics, molecular visualization and analysis, and network visualization and analysis. It also provides local access to up-to-date versions of sequence analysis software and sequence databases. As development continues, it is imperative that the RBVI team remains connected to the broader structural and molecular biology research and teaching community through outreach and training. These activities promote awareness of what the Resource has to offer, resulting in more effective use and driving further developments.